The goal of this project is to analyze the structure and function of arenaviruses at the molecular and antigenic level. Specific objectives include a detailed structural and antigenic analysis of the glycoproteins of LCM and Pichinde viruses in order to understand the assembly and diversity of these molecules. Analysis of persistent arenavirus infections will be directed toward determining the repertoire of immune responses to mice against persisting virus, and studying the changes that virus undergoes in the course of persistent disease. Molecular biology of the arenaviruses will be approached in two ways. First, we will study the structure and functions of gene products encoded on the 8-9 kb L RNA segment. Second, we will undertake molecular cloning of the Tacaribe virus, a virus which differs in fundamental biological and structural features from LCM and Pichinde viruses, in order to begin to understand the molecular basis for these differences. Arenaviruses are significant human pathogens on the African and South American continents. In addition, Lymphocytic Choriomeningitis virus has proven to be an extremely valuable and instructive laboratory model. The studies described in this application will provide basic information to interpret the biology, structure and evolution of the arenaviruses and will suggest rational strategies of diagnosis, therapy and prevention of arenavirus diseases of man.